Enhancing Stability of Liposome by Synergistic Effect of Polymer Multiple-units

Xian-cheng Tian; Yuan-chen Dong; Ya-wei Sun; Dong-sheng Liu

doi:10.11777/j.issn1000-3304.2022.22305

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Enhancing Stability of Liposome by Synergistic Effect of Polymer Multiple-units

Research Article | 更新时间：2024-01-18

- Enhancing Stability of Liposome by Synergistic Effect of Polymer Multiple-units
  增强出版
- ACTA POLYMERICA SINICA Vol. 54, Issue 5, Pages: 675-686(2023)
- 作者机构：
  
  1.稀土新材料教育部工程研究中心
  2.生命有机磷化学及化学生物学教育部重点实验室清华大学化学系北京 100084
  3.中国科学院化学研究所北京 100190
  4.中国石油大学（华东）化学工程学院青岛 258000
- 作者简介：
  
  Dong-sheng Liu, E-mail: liudongsheng@tsinghua.edu.cn
- 基金信息：
- DOI：10.11777/j.issn1000-3304.2022.22305
  CLC：
- Published：20 May 2023，
  
  Published Online：24 November 2022，
  
  Received：08 September 2022，
  
  Accepted：01 November 2022
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田显城,董原辰,孙亚伟等.利用高分子多基元协同效应增强脂质体稳定性的研究[J].高分子学报,2023,54(05):675-686.

Tian Xian-cheng,Dong Yuan-chen,Sun Ya-wei,et al.Enhancing Stability of Liposome by Synergistic Effect of Polymer Multiple-units[J].ACTA POLYMERICA SINICA,2023,54(05):675-686.
田显城,董原辰,孙亚伟等.利用高分子多基元协同效应增强脂质体稳定性的研究[J].高分子学报,2023,54(05):675-686. DOI： 10.11777/j.issn1000-3304.2022.22305.

Tian Xian-cheng,Dong Yuan-chen,Sun Ya-wei,et al.Enhancing Stability of Liposome by Synergistic Effect of Polymer Multiple-units[J].ACTA POLYMERICA SINICA,2023,54(05):675-686. DOI： 10.11777/j.issn1000-3304.2022.22305.

摘要

通过合成接枝胆固醇的壳聚糖水溶性高分子，并利用所接枝胆固醇的插膜能力，诱导高分子贴附于脂质体表面，形成高分子-脂质体复合物. 研究发现，壳聚糖水溶性高分子可以起到屏蔽膜表面电荷的作用，同时该体系利用高分子链上多位点修饰的疏水基团与磷脂分子之间的疏水作用和高分子多基元之间共价连接的协同效应，增强了脂质体的抗融合及抗表面活性剂能力. 该复合策略制备过程简便快捷，在体外实验中已展现出良好的稳定性，在长循环药物递送方面具有潜在的应用.

Abstract

We synthesized a water soluble glycol chitosan polymer grafted with cholesterol through substitution reaction

and the polymer was applied to form a polymer-liposome complex (PLC). According to dynamic light scattering (DLS) and transmission electron microscope (TEM) characterization

the diameter of the PLC was about 100 nm and the morphology was similar to the plain liposome. The cholesterol group can induce the polymer backbone to attach to the surface of the liposome membrane and the integration cability of the glycol chitosan-cholesterol (GCC) was characterized by laser confocal scanning microscope (LCSM). The zeta potential of the liposome containing negative charged phospholipid was -23.2 mV. With integration of the glycol chitosan-cholesterol

the zeta potential significantly increased to -1.78 mV

which indicated that the attached water-soluble polymer can shield the surface charge of the membrane. By encapsulating fluorescent molecules in the liposome or mixing fluorescent phospholipid during the lipid preparation process

fluorescence resonance energy transfer (FRET) experiment was introduced to test the stability of the PLC. Charge-induced liposome fusion occurred by adding positively charged ions or liposome into negatively charged liposome solution. The PLC has shown the ability to resist the fusion process which can keep the integrity and monodispersity of the liposome. However

the plain liposome was observed in aggregates visible to the naked eyes after adding hetero-charged ions in several minutes. The FRET variation results indicated that the addition of the GCC can slow down the hetero-charged liposome fusion process. In addition

the PLC can also protect against the liposome leakage induced by surfactant

which resulted from synergistic effect of polymer multiple-units. Incubated with 20% FBS under 37 ℃

the PLC showed well stability in 3 days

while the PDI and the size of the plain liposome were increased obviously during incubation. The preparation process of this polymer-liposome complex strategy is simple and fast

and it has shown good stability in

in vitro

experiments. This system has potential applications in long circulation drug delivery.

关键词

脂质体稳定性高分子复合物

Keywords

LiposomeStabilityPolymerComplex

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